Genome-wide localization of histone variants in Toxoplasma gondii implicates variant exchange in stage-specific gene expression.
Nardelli, S. C., Silmon de Monerri, N. C., Vanagas, L., Wang, X., Tampaki, Z., Sullivan, W. J., Jr., Angel, S. O. and Kim, K.
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Present address: Instituto Carlos Chagas/Fiocruz-PR, Curitiba, PR, CEP 81.350-010, Brazil.
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Present address: Pfizer Inc, Pearl River, NY, 10965, USA.
Laboratorio de Parasitologia Molecular, Instituto Tecnologico Chascomus (INTECH), Consejo Nacional de Investigaciones Cientificas (CONICET)-Universidad Nacional General San Martin (UNSAM), Chascomus, Argentina.
Department of Pathology, University of Cambridge, Cambridge, UK.
Present address: School of Public Health, Shanghai JiaoTong University, School of Medicine, Shanghai, China.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA.
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. kamikim@usf.edu.
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. kamikim@usf.edu.
Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. kamikim@usf.edu.
Department of Internal Medicine, Division of Infectious Disease and International Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA. kamikim@usf.edu.
BACKGROUND: Toxoplasma gondii is a protozoan parasite that differentiates from acute tachyzoite stages to latent bradyzoite forms in response to environmental cues that modify the epigenome. We studied the distribution of the histone variants CenH3, H3.3, H2A.X, H2A.Z and H2B.Z, by genome-wide chromatin immunoprecipitation to understand the role of variant histones in developmental transitions of T. gondii parasites. RESULTS: H3.3 and H2A.X were detected in telomere and telomere associated sequences, whereas H3.3, H2A.X and CenH3 were enriched in centromeres. Histones H2A.Z and H2B.Z colocalize with the transcriptional activation mark H3K4me3 in promoter regions surrounding the nucleosome-free region upstream of the transcription start site. The H2B.Z/H2A.Z histone pair also localizes to the gene bodies of genes that are silent but poised for activation, including bradyzoite stage-specific genes. The majority of H2A.X and H2A.Z/H2B.Z loci do not overlap, consistent with variant histones demarcating specific functional regions of chromatin. The extent of enrichment of H2A.Z/H2B.Z (and H3.3 and H2A.X) within the entire gene (5'UTR and gene body) reflects the timing of gene expression during the cell cycle, suggesting that dynamic turnover of H2B.Z/H2A.Z occurs during the tachyzoite cell cycle. Thus, the distribution of the variant histone H2A.Z/H2B.Z dimer defines active and developmentally silenced regions of the T. gondii epigenome including genes that are poised for expression. CONCLUSIONS: Histone variants mark functional regions of parasite genomes with the dynamic placement of the H2A.Z/H2B.Z dimer implicated as an evolutionarily conserved regulator of parasite and eukaryotic differentiation.
BMC Genomics 23(1): 128 (2022)